eMedicine Specialties > Infectious Diseases > Parasitic Infections
Malaria: Differential Diagnoses & Workup
Updated: Apr 29, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
| African Trypanosomiasis (Sleeping
Sickness) | Leptospirosis |
| Babesiosis | Typhoid Fever |
| Dengue Fever | |
| Ehrlichiosis | |
| Influenza |
Other Problems to Be Considered
HIV infection
Viral illness
Bacteremia
Workup
Laboratory Studies
A diagnosis of malaria should be supported by the identification of the parasites on a thin or thick blood smear. The only rare exception is P falciparum infection, in which all the parasites during the life cycle can be sequestered out of the peripheral blood in late-stage forms. If no alternative diagnosis is found in an at-risk patient with possible cerebral malaria (ie, unrevealing lumbar puncture findings), initiate therapy for presumptive malaria and continue to obtain additional blood smears to confirm the diagnosis. This is not an occult infection.
Malaria should be suspected in patients with a malarialike illness, including thrombocytopenia, relative lymphopenia, atypical lymphocytes, and an elevated lactate dehydrogenase (LDH) level.
- Thick smears
- Three thick and thin smears 12-24 hours apart should be obtained. The highest yield of peripheral parasites occurs during or soon after a fever spike; however, smears should not be delayed while awaiting fever spikes.
- Thick smears are 20 times more sensitive than thin smears, but speciation may be more difficult. The parasitemia can be calculated based on the number of infected RBCs. This is a quantitative test.
- Thin smears
- Thin smears are less sensitive than thick smears but facilitate speciation. This should be considered a qualitative test.
- Treatment greatly depends on the identification of the Plasmodium species responsible for the infection.
- Alternative diagnostic methods
- Alternative diagnostic methods typically are used if the laboratory does not have sufficient expertise in detecting parasites in blood smears.
- The quantitative buffy coat (QBC) is a technique that is as sensitive as thick smears. Because results cannot be used to speciate Plasmodium, a thin smear must be examined.
- Monoclonal antibody to histidine-rich protein-2 (ParaSight-F, immunochromatographic test [ICT]) appears to be very sensitive and specific.
- A rapid dipstick test that detects LDH of the parasite (eg, OptiMal) can also be used to distinguish P falciparum from the other species. This is particularly useful if laboratory expertise in differentiating the species is lacking. Similar to blood smears, these rapid tests may provide false-negative results in patients with very low parasitemia and should be repeated if results are initially negative and the diagnosis remains unknown.
- In addition to the rapid diagnostic test listed above (eg, QBC, OptiMal), new molecular techniques such as polymerase chain reaction (PCR) and nucleic acid sequence-based amplification (NASBA) are also available for diagnosis. They are more sensitive than thick smears but are expensive and unavailable in most developing countries.3
- Malaria is a reportable disease. Identification of parasites by any of the above techniques should prompt notification to the local or state health department.
- Blood tests
- In returning travelers, malaria is suggested by the triad of thrombocytopenia, elevated LDH levels, and atypical lymphocytes. These findings should prompt obtaining malarial smears.
- In general, blood cultures should be drawn in a febrile patient. Typhoid is often part of the differential diagnoses in patients returning from tropical areas. In addition, patients from tropical areas may have more than one infection; maintaining a high suspicion for additional infections should be considered when patients do not respond to antimalarials.
- Hypoglycemia may occur in patients with malarial infection and should be ruled out in patients with mental-status changes.
- Assess hemoglobin (decreased in 25%, often profoundly in young children), platelet counts (thrombocytopenia in 50-68%), and liver function (results abnormal in 50%). Also monitor renal function, electrolytes (especially sodium), and parameters suggestive of hemolysis (haptoglobin, LDH, reticulocyte count).
- Importantly, fewer than 5% of patients with malaria have an elevated WBC count. If leukocytosis is present, the examiner should entertain a broader list of differential diagnoses.
- If the patient is to be treated with primaquine, a glucose-6-phosphate dehydrogenase (G-6-PD) level should be obtained because primaquine can result in severe hemolysis in these patients.
- If the patient has cerebral malaria, obtain a blood glucose level to rule out hypoglycemia as a cause of mental-status changes. Note that intravenous quinine can induce hypoglycemia; therefore, blood glucose should be monitored when intravenous quinine is used.
Procedures
- If the patient exhibits mental-status changes, and even if the peripheral smear demonstrates P falciparum, a lumbar puncture should be performed to rule out bacterial meningitis.
Histologic Findings
Histologic Variations Among Plasmodium Species
Open table in new window
Table
| Findings | P falciparum | P vivax | P ovale | P malariae |
| Only early forms present in peripheral blood | Yes | No | No | No |
| Multiply-infected RBCs | Often | Occasionally | Rare | Rare |
| Age of infected RBCs | RBCs of all ages | Young RBCs | Young RBCs | Old RBCs |
| Schüffner dots | No | Yes | Yes | No |
| Other features | Cells have thin cytoplasm, 1 or 2 chromatin dots, and applique forms. | Late trophozoites develop pleomorphic cytoplasm. | Infected RBCs become oval with tufted edges. | Bandlike trophozoites are distinctive. |
| Findings | P falciparum | P vivax | P ovale | P malariae |
| Only early forms present in peripheral blood | Yes | No | No | No |
| Multiply-infected RBCs | Often | Occasionally | Rare | Rare |
| Age of infected RBCs | RBCs of all ages | Young RBCs | Young RBCs | Old RBCs |
| Schüffner dots | No | Yes | Yes | No |
| Other features | Cells have thin cytoplasm, 1 or 2 chromatin dots, and applique forms. | Late trophozoites develop pleomorphic cytoplasm. | Infected RBCs become oval with tufted edges. | Bandlike trophozoites are distinctive. |
More on Malaria |
| Overview: Malaria |
 Differential Diagnoses & Workup: Malaria |
| Treatment & Medication: Malaria |
| Follow-up: Malaria |
| References |
| « Previous Page | Next Page » |
References
Cox-Singh J, Davis TM, Lee KS, Shamsul SS, Matusop A, Ratnam S, et al. Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening. Clin Infect Dis. Jan 15 2008;46(2):165-71. [Medline].
CDC information website for malaria. Available at http://www.cdc.gov/malaria/.
Mens P, Spieker N, Omar S, et al. Is molecular biology the best alternative for diagnosis of malaria to microscopy? A comparison between microscopy, antigen dectection and molecular tests in rural Kenya and urban Tanzania. Trop Med Int Health. Feb/2007;2:238-44. [Medline]. [Full Text].
Poespoprodjo JR, Fobia W, Kenangalem E, Lampah DA, Warikar N, Seal A, et al. Adverse pregnancy outcomes in an area where multidrug-resistant plasmodium vivax and Plasmodium falciparum infections are endemic. Clin Infect Dis. May 1 2008;46(9):1374-81. [Medline].
Ashley EA, White NJ. Artemisinin-based combinations. Curr Opin Infect Dis. Dec 2005;18(6):531-6. [Medline].
Baird JK, Hoffman SL. Prevention of malaria in travelers. Med Clin North Am. Jul 1999;83(4):923-44, vi. [Medline].
Croft A. Extracts from "Clinical Evidence." Malaria: prevention in travelers. BMJ. Jul 15 2000;321(7254):154-60. [Medline].
Cunha BA. Malaria or typhoid fever: a diagnostic dilemma?. Am J Med. Dec 2005;118(12):1442-3; author reply 1443-4. [Medline].
Cunha BA. The diagnosis of imported malaria. Arch Intern Med. Aug 13-27 2001;161(15):1926-8. [Medline].
Cunha BA. The Importance of non-specific laboratory tests in suspecting malaria in returning US travelers. Ann Intern Med. 2004;14:e141/7/547.
Cunha BA. Triad of non-specific laboratory tests in malaria. Scand J Infect Dis. 2008;40(4):350-1. [Medline].
Dorsey G, Gandhi M, Oyugi JH, Rosenthal PJ. Difficulties in the prevention, diagnosis, and treatment of imported malaria. Arch Intern Med. Sep 11 2000;160(16):2505-10. [Medline].
Eliades MJ, Shah S, Nguyen-Dinh P, et al. Malaria surveillance--United States, 2003. MMWR Surveill Summ. Jun 3 2005;54(2):25-40. [Medline].
Froude JR, Weiss LM, Tanowitz HB, Wittner M. Imported malaria in the Bronx: review of 51 cases recorded from 1986 to 1991. Clin Infect Dis. Nov 1992;15(5):774-80. [Medline].
Idro R, Jenkins NE, Newton CR. Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurol. Dec 2005;4(12):827-40. [Medline].
Kain KC, Harrington MA, Tennyson S. Imported malaria: prospective analysis of problems in diagnosis and management. Clin Infect Dis. Jul 1998;27(1):142-9. [Medline].
Kain KC, Harrington MA, Tennyson S, Keystone JS. Imported malaria: prospective analysis of problems in diagnosis and management. Clin Infect Dis. Jul 1998;27(1):142-9. [Medline].
Kain KC, Keystone JS. Malaria in travelers. Epidemiology, disease, and prevention. Infect Dis Clin North Am. Jun 1998;12(2):267-84. [Medline].
Mandell G, Bennet J, Dolin R. Plasmodium species (malaria). In: Principles and Practice of Infectious Diseases. Vol 2. 6th ed. Elsevier; 2005:Chapter 272.
Marsh K, Forster D, Waruiru C, et al. Indicators of life-threatening malaria in African children. N Engl J Med. May 25 1995;332(21):1399-404. [Medline].
Plowe CV. Antimalarial drug resistance in Africa: strategies for monitoring and deterrence. Curr Top Microbiol Immunol. 2005;295:55-79. [Medline].
Schlagenhauf-Lawlor P. Use of rapid malaria test for and by travelers. In: Traveler's Malaria. B.C. Decker Inc.; 2001:Chapter 13.
Schlossberg D. Malaria--treatment and prophylaxis. In: Current Therapy of Infectious Diseases. Mosby; 2001.
White NJ. Antimalarial drug resistance. J Clin Invest. Apr 2004;113(8):1084-92. [Medline].
Wiest PM, Opal SM, Romulo RL, Olds GR. Malaria in travelers in Rhode Island: a review of 26 cases. Am J Med. Jul 1991;91(1):30-6. [Medline].
Winters RA, Murray HW. Malaria--the mime revisited: fifteen more years of experience at a New York City teaching hospital. Am J Med. Sep 1992;93(3):243-6. [Medline].
Further Reading
Keywords
malaria, blackwater fever, tertian fever, quartan fever, jungle fever, airport malaria, Anopheles mosquito, Plasmodium falciparum, P falciparum, Plasmodium vivax, P vivax, Plasmodium ovale, P ovale, Plasmodium malariae, P malariae, Plasmodium knowlesi, P knowlesi, paludismo
